EU/3/13/1117: Orphan designation for the treatment of Stargardt's disease

Stargardt's disease is a genetic (hereditary) disorder of the eye that leads to progressive loss of sight. Stargardt's disease is caused by abnormalities in a gene called ABCA4. The ABCA4 gene is responsible for the production of a protein called ABCR that regulates the transport of substances in and out of some cells in the retina (the light-sensitive surface at the back of the eye). In patients with Stargardt's disease, ABCR does not work properly. This causes deposits to build up inside the retina cells, which become damaged and eventually die.

Stargardt's disease is a long-term debilitating disease because the patient's sight becomes progressively worse and eventually leads to blindness.

At the time of designation, Stargardt's disease affected approximately 1.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 61,100 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 509,000,000 (Eurostat 2013).

At the time of submission of the application for orphan designation, no satisfactory methods were authorised in the EU for the treatment of Stargardt's disease. Patients with the disease were usually given physical aids such as sunglasses to reduce the rate of damage to the retina, or spectacles, magnifiers or telescopes to help them see during the early stages of the disease. Laser treatment can help to stabilise the loss of vision in some patients.

Ramiprilat is an angiotensin-converting-enzyme (ACE) inhibitor. ACE inhibitors have several actions in the body, one of which is reducing the breakdown of a substance called bradykinin. This in turn results in increased release of nitric oxide, a substance which is known to protect nerve cells from damage, including retina cells. ACE inhibitors may also help reduce damage to cells in the retina by reducing the formation of toxic forms of oxygen called free radicals. Ramiprilat is expected to be given as eye drops.

The effects of ramiprilat have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with ramiprilat in patients with Stargardt's disease had been started.

At the time of submission, ramiprilat was not authorised anywhere in the EU for Stargardt's disease or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 2013 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.